Regulation of stress susceptibility by chromatin-binding protein PHF6 in the pituitary intermediate lobe.

ABSTRACT: The pituitary intermediate lobe (IL) is a surprisingly understudied pituitary region. Here, we find that chromatin-binding protein PHF6 is enriched in the pituitary IL and plays a crucial role in regulating stress susceptibility in mice. Conditional knockout of Phf6 in PHF6-positive IL cells (^ILPHF6 cells) significantly reduces acute stress-induced anxiety-like behaviors and chronic stress-induced depression-like behaviors by impairing cellular activation and the release of stress-related hormones. Mechanistically, conditional knockout of Phf6 in the pituitary IL cells downregulates the calcium channel β3 subunit and suppresses transcription of stress-responsive genes. Chemogenetic inhibition of ^ILPHF6 cells reduces stress susceptibility, whereas activation of these c

SUBMITTER: Liu B 

PROVIDER: S-EPMC12916324 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature